In Vitro and Clinical Evaluations of the Drug-Drug Interaction Potential of a Metabotropic Glutamate 2/3 Receptor Agonist Prodrug with Intestinal Peptide Transporter 1

ABSTRACT Despite peptide transporter 1 (PEPT1) being responsible for the bioavailability for a variety of drugs, there has been little study of its potential involvement in drug-drug interactions. Pomaglumetad methionil, a metabotropic glutamate 2/3 receptor agonist prodrug, utilizes PEPT1 to enhance absorption and bioavailability. In vitro studies were conducted to guide the decision to conduct a clinical drug interaction study and to inform the clinical study design. In vitro investigations determined the prodrug (LY2140023 monohydrate) is a substrate of PEPT1 with K m value of approximately 30 mM, whereas the active moiety (LY404039) is not a PEPT1 substrate. In addition, among the eight known PEPT1 substrates evaluated in vitro, valacyclovir was the most potent inhibitor (IC 50 = 0.46 mM) of PEPT1-mediated uptake of the prodrug. Therefore, a clinical drug interaction study was conducted to evaluate the potential interaction between the prodrug and valacyclovir in healthy subjects. No effect of coadministration was observed on the pharmacokinetics of the prodrug, valacyclovir, or either of their active moieties. Although in vitro studies showed potential for the prodrug and valacyclovir interaction via PEPT1, an in vivo study showed no interaction between these two drugs. PEPT1 does not appear to easily saturate because of its high capacity and expression in the intestine. Thus, a clinical interaction at PEPT1 is unlikely even with a compound with high affinity for the transporter

Small Scale Collaborative Services: The Role of Design in the Development of the Human Smart City Paradigm

Cities are facing disruptive challenges today. All these require smarter solutions and are creating pressure for the public and private sector to deliver innovative services and great expectations are put in the new Smart City paradigm. Most of these solutions keep technologies out of the urban environments, far from being considered components of the urban functioning and, furthermore, even farer from people and their urban spaces. In this framework design is today re-orienting its theories and practices to new kind of design contexts (neighborhoods, streets, squares, cities) where societal challenges are emerging that require different level of changes from everyday life to huge public institutions and complex organizations. This re-orientation is based on a different smart city paradigm that puts people at the center of the cities smartness and recognizes the need for developing micro and contextualized solutions to address larger cities problems in a sociable mode

Foregrounding Learning in Infrastructuring : to Change Worldviews and Practices in the Public Sector

Mutual learning and infrastructuring are two core concepts in Participatory Design (PD), but the relation between them has yet to be explored. In this article, we foreground learning in infrastructuring processes aimed at change in the public sector. Star and Ruhleder’s (1996) framework for first, second, and third level issues is applied as a fruitful way to stage and analyze learning in such processes. The argument is developed through the insights that arose from a 4-year-long infrastructuring process about future library practices. Framed as Co-Labs this process was organized by researchers and officers from the local regional office. This led to adjusted roles for both PD researchers and civil servants working with materials at the operational and strategic levels. The case shows how learning led to profound changes in the regional public sector in the form of less bureaucratic and more participatory experimental and learning-focused worldviews and practices.Urb@ExpSocial Innovation Skån

Italianway: An Entrepreneurial Innovation for Hospitality in Contemporary Cities

This chapter is devoted to a specific case of sharing economy in Milan, broadening the vision to include the influence that infrastructuring processes have not only on the complex socio-technical system (scale-up) but also on a single case at local level (scale-down), supporting the authors in a reflection of the impact of the sharing economy on management innovation. We describe Italianway, a Milanese platform that links visitors with the local communities and services to offer an authentic experience of the city; in the creators’ words: “Live like a local, welcome to Milan”. This chapter illustrates the favourable factors of the wider contemporary scenario on local economic growth, enabling the introduction of innovative solutions into a traditional economic system through the hybridisation of the sharing economy approach with and within a given milieu

Spatial and Service Design: Guidelines Defining University Dormitories

Thispapercontributestothediscussionaboutrelationshipsbetween spatial and service design and how these two disciplines can interact and influence each other to achieve more complexity, capability and synergy in in a specific case such as university dormitories. Dormitories, university campuses, and schools, can be considered as urban community hubs through which syn- ergistic relations between the institution and the surrounding neighborhood take place. The paper investigates how dormitories can, starting with the contribution of the students, perform strategic actions in the socio-cultural and civil regen- eration of urban contexts. The aim is to delineate the various interactions and effective synergies, especially in relation to the most vulnerable and marginal- ized facets of the community, looking at the students’ dorm as places of social cohesion. The methodology is related to community-centered design using for example co-design tools to present relationships between spatial and service design particularly through the context of a collaborative design studio and the technical department of Politecnico di Milano

Designing solutions for the commons

The regeneration of the commons occurs through direct involvement of groups of people who interact closely with spaces, and who aim to improve the overall quality of life and experiences connected with those spaces. This process starts from an increased consciousness towards places that do not belong to the private realm but are public or can potentially be used by the society Revealing the commons means being aware of the potentialities of these “hidden places” to not only connect people with them, but for people to also create a previously unknown sense of community and ownership among themselves. By showing best practices developed by the Polimi DESIS Lab in the city of Milan and its surroundings, this paper reveals: how design relates to this process; the relationship between the time of involvement and the effectiveness of the results the short- and long-term impacts of these interventions; and the legacy of the regeneration, including both failures and successes